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The British Journal of Dermatology Sep 2023On the basis of safety data for patients with inflammatory rheumatism or inflammatory bowel disease, treatment with Janus kinase (JAK) inhibitors (JAKi) has been linked... (Meta-Analysis)
Meta-Analysis
BACKGROUND
On the basis of safety data for patients with inflammatory rheumatism or inflammatory bowel disease, treatment with Janus kinase (JAK) inhibitors (JAKi) has been linked to the occurrence of major adverse cardiovascular events (MACE). However, these inflammatory diseases are proatherogenic; in contrast, patients with atopic dermatitis (AD) do not usually have a high cardiovascular (CV) comorbidity burden.
OBJECTIVES
To perform a systematic review and meta-analysis of MACE in patients with AD treated with JAKi.
METHODS
We systematically searched PubMed, Embase, Cochrane Library and Google Scholar from their inception to 2 September 2022. Cohort studies, randomized controlled trials and pooled safety analyses providing CV safety data on patients taking JAKi for AD were selected. We included patients aged ≥ 12 years. We built a 'controlled-period' cohort (n = 9309; 6000 exposed to JAKi and 3309 exposed to comparators) and an 'all-JAKi' cohort (n = 9118 patients exposed to a JAKi in any of the included studies). The primary outcome was a composite of acute coronary syndrome (ACS), ischaemic stroke and CV death. The broader secondary MACE outcome encompassed ACS, stroke (whether ischaemic or haemorrhagic), transient ischaemic attack and CV death. The frequency of primary and secondary MACE was assessed in both cohorts. A fixed-effects meta-analysis using the Peto method was used to calculate the odds ratio (OR) for MACE in the 'controlled-period' cohort. Evaluation of the risk of bias was done using the Cochrane risk-of-bias tool (version 2). Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
RESULTS
Eight per cent of the records identified initially met the selection criteria, corresponding to 23 records included in the 'all-JAKi' cohort. Patients had been exposed to baricitinib, upadacitinib, abrocitinib, ivarmacitinib, placebo or dupilumab. Four primary events (three with JAKi and one with placebo) and five secondary events (four with JAKi and one with placebo) occurred among 9309 patients in the 'controlled-period' cohort (MACE frequency 0.04% and 0.05%, respectively). Eight primary events and 13 secondary events occurred among 9118 patients in the 'all-JAKi' cohort (MACE frequency 0.08% and 0.14%, respectively). The OR for primary MACE in patients with AD treated with JAKi vs. placebo or dupilumab was 1.35 (95% confidence interval 0.15-12.21; I2 = 12%, very low certainty of evidence).
CONCLUSIONS
Our review highlights rare cases of MACE among JAKi users for AD. JAKi may have little-to-no effect on the occurrence of MACE in patients with AD vs. comparators, but the evidence is uncertain. Real-life long-term population-level safety studies are needed.
Topics: Humans; Janus Kinase Inhibitors; Dermatitis, Atopic; Brain Ischemia; Stroke; Inflammatory Bowel Diseases
PubMed: 37410552
DOI: 10.1093/bjd/ljad229 -
BioDrugs : Clinical Immunotherapeutics,... Feb 2018The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern. (Review)
Review
BACKGROUND
The efficacy, safety and immunogenicity risk of switching between an originator biologic and a biosimilar or from one biosimilar to another are of potential concern.
OBJECTIVES
The aim was to conduct a systematic literature review of the outcomes of switching between biologics and their biosimilars and identify any evidence gaps.
METHODS
A systematic literature search was conducted in PubMed, EMBASE and Cochrane Library from inception to June 2017. Relevant societal meetings were also checked. Peer-reviewed studies reporting efficacy and/or safety data on switching between originator and biosimilar products or from one biosimilar to another were selected. Studies with fewer than 20 switched patients were excluded. Data were extracted on interventions, study population, reason for treatment switching, efficacy outcomes, safety and anti-drug antibodies.
RESULTS
The systematic literature search identified 63 primary publications covering 57 switching studies. The reason for switching was reported as non-medical in 50 studies (23 clinical, 27 observational). Seven studies (all observational) did not report whether the reasons for switching were medical or non-medical. In 38 of the 57 studies, fewer than 100 patients were switched. Follow-up after switching went beyond 1 year in eight of the 57 studies. Of the 57 studies, 33 included statistical analysis of disease activity or patient outcomes; the majority of these studies found no statistically significant differences between groups for main efficacy parameters (based on P < 0.05 or predefined acceptance ranges), although some studies observed changes for some parameters. Most studies reported similar safety profiles between groups.
CONCLUSIONS
There are important evidence gaps around the safety of switching between biologics and their biosimilars. Sufficiently powered and appropriately statistically analysed clinical trials and pharmacovigilance studies, with long-term follow-ups and multiple switches, are needed to support decision-making around biosimilar switching.
Topics: Biosimilar Pharmaceuticals; Humans
PubMed: 29344876
DOI: 10.1007/s40259-017-0256-z -
Biomarker Insights 2023The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years,... (Review)
Review
BACKGROUND
The use of biomarkers varies from disease etiognosis and diagnosis to signal detection, risk prediction, and management. Biomarker use has expanded in recent years, however, there are limited reviews on the use of biomarkers in pharmacovigilance and specifically in the monitoring and management of adverse drug reactions (ADRs).
OBJECTIVE
The objective of this manuscript is to identify the multiple uses of biomarkers in pharmacovigilance irrespective of the therapeutic area.
DESIGN
This is a systematic review of the literature.
DATA SOURCES AND METHODS
Embase and MEDLINE database searches were conducted for literature published between 2010-March 19, 2021. Scientific articles that described the potential use of biomarkers in pharmacovigilance in sufficient detail were reviewed. Papers that did not fulfill the United States Food and Drug Administration (US FDA) definition of a biomarker were excluded, which is based on the International Conference on Harmonisation (ICH)-E16 guidance.
RESULTS
Twenty-seven articles were identified for evaluation. Most articles involved predictive biomarkers (41%), followed by safety biomarkers (38%), pharmacodynamic/response biomarkers (14%), and diagnostic biomarkers (7%). Some articles described biomarkers that applied to multiple categories.
CONCLUSION
Various categories of biomarkers including safety, predictive, pharmacodynamic/response, and diagnostic biomarkers are being investigated for potential use in pharmacovigilance. The most frequent potential uses of biomarkers in pharmacovigilance in the literature were the prediction of the severity of an ADR, mortality, response, safety, and toxicity. The safety biomarkers identified were used to evaluate patient safety during dose escalation, identify patients who may benefit from further biomarker testing during treatment, and monitor ADRs.
PubMed: 37077840
DOI: 10.1177/11772719231164528 -
International Journal of Cardiology.... Feb 2023The scope of this systematic review is to update the existing body of evidence regarding the cost-effectiveness of transcatheter aortic valve implantation, stratified... (Review)
Review
OBJECTIVE
The scope of this systematic review is to update the existing body of evidence regarding the cost-effectiveness of transcatheter aortic valve implantation, stratified across all risk categories, and to assess their methodological quality.
METHODS
A systematic review was performed including published cost-effectiveness analyses of heart valve implantations. The quality was assessed with the Quality of Health Economics Tool.
RESULTS
We identified 33 economic evaluations of transcatheter aortic heart valve implantations. Results were not consistent, ranging from dominant to dominating. Moreover, the models were sensitive to an array of variables. The methodological quality of the studies was good.
CONCLUSION
This systematic review led to inconclusive and inconsistent results pertinent to the economic profile of TAVI technology. It also highlighted areas which merit further research regarding the pillars of cost-effectiveness analysis such as modeling, the extrapolation of available data and the uncertainty of the evidence. A thorough assessment of the patient should proceed any decision-making.
PubMed: 36747880
DOI: 10.1016/j.ijcha.2023.101173 -
Pharmaceutics Jan 2022Pharmacovigilance is a science that involves the ongoing monitoring of adverse drug reactions to existing medicines. Traditional approaches in this field can be... (Review)
Review
Pharmacovigilance is a science that involves the ongoing monitoring of adverse drug reactions to existing medicines. Traditional approaches in this field can be expensive and time-consuming. The application of natural language processing (NLP) to analyze user-generated content is hypothesized as an effective supplemental source of evidence. In this systematic review, a broad and multi-disciplinary literature search was conducted involving four databases. A total of 5318 publications were initially found. Studies were considered relevant if they reported on the application of NLP to understand user-generated text for pharmacovigilance. A total of 16 relevant publications were included in this systematic review. All studies were evaluated to have medium reliability and validity. For all types of drugs, 14 publications reported positive findings with respect to the identification of adverse drug reactions, providing consistent evidence that natural language processing can be used effectively and accurately on user-generated textual content that was published to the Internet to identify adverse drug reactions for the purpose of pharmacovigilance. The evidence presented in this review suggest that the analysis of textual data has the potential to complement the traditional system of pharmacovigilance.
PubMed: 35213998
DOI: 10.3390/pharmaceutics14020266 -
Antidepressants and Vertebral and Hip Risk Fracture: An Updated Systematic Review and Meta-Analysis.Healthcare (Basel, Switzerland) Apr 2022Although antidepressant drugs appear to play an active role in increasing fracture risk, their weight is still unclear. We conducted a PRISMA compliant systematic review... (Review)
Review
Although antidepressant drugs appear to play an active role in increasing fracture risk, their weight is still unclear. We conducted a PRISMA compliant systematic review and meta-analysis through PubMed/Scopus/Cochrane libraries and registered with PROSPERO (registration number CRD42021254006) to investigate the relationship between antidepressant drugs categories, including SSRIs, SNRIs, and TCAs, and the risk of hip and vertebral fractures. After screening 3122 items, we finally found 26 papers for qualitative analysis and 11 for quantitative synthesis. A total of 15,209,542 adult and elderly patients were identified, with a mean follow-up of 51 months and a major prevalence of women. We identified results largely for SSRIs, with only a small amount of data for SNRIs, TCAs, and NaSSA. No data were found among the most recent categories of antidepressants, such as vortioxetine and esketamine. All included studies reported hip fractures, while three of them also included vertebral fractures. Overall, we observed a significant effect of SSRIs on fracture risk with a mean effect of 0.98 (95% CI = 0.75-1.20). This meta-analysis reveals that the use of SSRIs increases the risk of fractures. Clinicians' awareness in antidepressant prescription should optimize their potential while reducing this risk.
PubMed: 35627940
DOI: 10.3390/healthcare10050803 -
Phytotherapy Research : PTR Mar 2022This systematic review and meta-analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase,... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis were conducted to determine the effects of anthraquinone (AQ) laxatives on colorectal cancer (CRC). We searched PubMed, Embase, Google Scholar, and CENTRAL from inception until March 2021, for randomized controlled trials (RCTs) and observational studies. Through the systematic review, we identified 8 observational studies evaluating AQ laxatives use as a risk factor for CRC development, and 5 studies on CRC risk were included in the meta-analysis using a random-effects model. Through the meta-analysis, we found that a history of AQ laxatives use compared with "other" and "no laxatives" use was associated with CRC development (OR: 1.41; 95% CI: 0.94-2.11), although not at a statistically significant level. The possible association persists even after removal of the outlier studies (OR: 1.51; 95% CI: 0.97-2.34). Selection of cases and controls was judged at low or unclear risk of bias across almost all studies, and the quality of evidence was from moderate to low. In conclusion, it is not possible to associate the use of AQ laxatives with the development of CRC. However, the trend toward an increased risk of CRC provides a strong indication for investigating this issue by performing further high-quality studies.
Topics: Anthraquinones; Colorectal Neoplasms; Constipation; Humans; Laxatives
PubMed: 35040201
DOI: 10.1002/ptr.7373 -
Frontiers in Psychiatry 2023Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its... (Review)
Review
The potential effect of metformin on cognitive and other symptom dimensions in patients with schizophrenia and antipsychotic-induced weight gain: a systematic review, meta-analysis, and meta-regression.
INTRODUCTION
Metformin has shown good efficacy in the management of antipsychotic-induced metabolic syndrome (MetS) in patients with schizophrenia or schizoaffective disorders. Its ability to induce antidepressant behavioural effects and improve cognitive functions has also been investigated: yet information has not been systematized. The aim of this study was therefore to investigate the effects of metformin on cognitive and other symptom dimension in schizophrenic patients treated with antipsychotics through a systematic review and meta-analysis.
METHODS
We searched PubMed, ClinicalTrials.Gov, Embase, PsycINFO, and WHO ICTRP database up to February 2022, Randomised Controlled Trials (RCT) evaluating patients diagnosed with schizophrenia and related disorders, who were treated with metformin as add-on therapy to antipsychotics for the treatment of weight gain and in which changes in psychiatric symptoms and cognitive functions were evaluated.
RESULTS
A total of 19 RCTs met the inclusion criteria. Meta-analysis was performed on 12 eligible studies. We found a positive trend after 24 weeks of treatment in schizophrenic patients with stable conditions [SMD (95%CI) = -0.40 (-0.82;0.01), OR (95%CI) = 0.5 (-2.4;3.4)]. Better performance was detected in the Brief Assessment of Cognition in Schizophrenia and Positive and Negative Syndrome Scale (PANSS) with low heterogeneity among studies. One study reported changes in BACS-verbal memory subdomain in favour of placebo [MD (95%CI) = -16.03 (-23.65;8.42)]. Gastrointestinal disorders, xerostomia, and extrapyramidal syndrome were the most reported adverse effects. Psychiatric adverse events were also described: in particular, symptoms attributable to a relapse of schizophrenia.
CONCLUSION
Some degree of efficacy was found for Metformin in improving cognitive and other symptom dimensions in patients with Schizophrenia. Given the clinical relevance of this potential pharmacological effect, longer specific studies using adequate psychometric scales are strongly recommended. Likewise, how metformin acts in this context needs to be evaluated in order to enhance its efficacy or find more efficacious drugs.
PubMed: 37502816
DOI: 10.3389/fpsyt.2023.1215807 -
Expert Opinion on Drug Safety Jan 2023This study aimed at providing pooled estimates of the incidence of adverse drug reactions (ADRs) of ubrogepant and rimegepant and to use meta-regression to identify... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study aimed at providing pooled estimates of the incidence of adverse drug reactions (ADRs) of ubrogepant and rimegepant and to use meta-regression to identify correlations between the occurrence of selected ADRs, socio-demographic, and clinical characteristics from data published in clinical studies.
METHODS
Ovid MEDLINE (up to 03/02/2022) was searched along with the references listed in the reviews identified with the research query. Random intercept and slope logistic regression models were used to estimate the logit transformation of the pooled incidence. To examine how selected clinical and socio-demographic characteristics correlated with the pooled incidence rates, we performed random-effects meta-regression.
RESULTS
Significant heterogeneity of incidence estimates was observed in clinical studies along with correlations between ADRs and the sociodemographic and clinical characteristics of patients exposed to ubrogepant. In particular, we observed a correlation between ubrogepant dosage and muscle strain and between Body Mass Index (BMI) and liver function values. For rimegepant, significant correlations were observed between age and infections and having aura symptoms at baseline and nausea/dizziness/diarrhea/muscle strain.
CONCLUSION
This study provided pooled incidence estimates of ubrogepant and rimegepant's ADRs and highlighted new safety aspects of the pharmacological treatment with ubrogepants and rimigepants from correlations obtained from the meta-regression.
Topics: Humans; Pyridines; Piperidines; Pyrroles; Drug-Related Side Effects and Adverse Reactions
PubMed: 36737057
DOI: 10.1080/14740338.2023.2177270 -
A systematic review and meta-analysis of vitamin D and calcium in preventing osteoporotic fractures.Clinical Rheumatology Dec 2020To assess and update the effect of the combination of vitamin D and calcium in the reduction of osteoporotic fractures, a systematic review across Cochrane Database,... (Meta-Analysis)
Meta-Analysis Review
To assess and update the effect of the combination of vitamin D and calcium in the reduction of osteoporotic fractures, a systematic review across Cochrane Database, NIHR HTA database, PubMed and Google Scholar was performed using mesh terms : Cohort studies OR Prospective Studies OR Longitudinal Studies OR Follow-Up Studies OR Incidence OR Risk OR Rate and Osteoporotic Fractures OR Fractures, Bone OR Fractures, Spontaneous OR Spinal Fractures OR Humeral Fractures OR Hip Fractures OR Femoral Neck Fractures AND Vitamin D AND Calcium and key words: vitamin D, fractures, osteoporosis, calcium, dietary supplements. Statistical analysis was performed with Review Manager (RevMan 5.3) using relative risk and confidence interval 95%. The combination reduced total fractures and hip fractures while no effect was observed in wrist fractures. The combination was also well tolerated. Only minor side effects were reported. This systematic review suggests that the combination of vitamin D and calcium can exert a beneficial effect towards osteoporotic fracture reduction.
Topics: Calcium; Calcium, Dietary; Dietary Supplements; Humans; Osteoporotic Fractures; Prospective Studies; Vitamin D
PubMed: 32447604
DOI: 10.1007/s10067-020-05122-3